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EC number: 204-701-4 | CAS number: 124-43-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- publication
- Title:
- Toxicological studies of urea. Acute, subacute and chronic tests in rats and mice.
- Author:
- Sato N, Aikawa K, Sugimoto T, Kotera K, Tauchi K, Tanaka H, IIkada K, and Igarashi N
- Year:
- 1 977
- Bibliographic source:
- Oyo Yakuri (Pharmacometrics) 13(5): 749-772
- Report date:
- 1977
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Subchronic and subacute dermal toxicity of urea. Exposure peridod 4 weeks and 25 weeks
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Urea
- EC Number:
- 200-315-5
- EC Name:
- Urea
- Cas Number:
- 57-13-6
- Molecular formula:
- CH4N2O
- IUPAC Name:
- urea
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- CAS number: 57-13-6
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Not speciified
Administration / exposure
- Type of coverage:
- not specified
- Vehicle:
- other: ointment
- Details on exposure:
- Test material was placed on the back skin. Area approx. 4 cm x 5 cm = 20 cm².
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 weeks and 25 weeks
- Frequency of treatment:
- 7/7 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- controls
- Dose / conc.:
- 54 mg/kg bw/day
- Remarks:
- Concentration: 10 % urea in ointment
- Dose / conc.:
- 108 mg/kg bw/day
- Remarks:
- Concentration: 20 % urea in ointment
- Dose / conc.:
- 216 mg/kg bw/day
- Remarks:
- Concentration: 40% urea in ointment
- No. of animals per sex per dose:
- 4 week study: 15 per sex and dose
25 week study: 10 per sex and dose - Control animals:
- yes
- not specified
- Details on study design:
- Urea conatining ointment was applied to the dorsal rat skin for 4 or 25 weeks, approx 542.4 mg each time. The treated area size was 5x4 cm. The urea concentrations used were 0, 10, 20, and 40%.
- Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: at termination
BODY WEIGHT: Yes
- Time schedule for examinations: once per week
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination
URINALYSIS: yes
- Time schedule: at termination
CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: No data
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: at least at termination
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/day: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION: Yes
- Time schedule for examinations: 4-week study: every 4 days; 25-week study: weekly
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 4-week study: 13 per dose group
- Parameters checked in table s 12-15 were examined:
red and white blood cell numbers, haematocrit.
Differential leucocyte count: eosinophils, neutrophils, monocytes in the 4- and the 25-week studies
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination
- Animals fasted: No data
- How many animals: probably all, but not specified
- Parameters checked in tables 16-19 for animals of the 4-and 25-week studies were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: at termination, prior to blood collection
- Metabolism cages used for collection of urine: No
- Animals fasted: No data
- Parameters checked in tables No. 8-11 were examined for animals of the 4-week and the 25-week studies
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER:
- organ weights: liver, brain, heart, spleen, kidneys, pituitary gland, thyroid, thymus, adrenal, ovary, uterus. See Tables No. 20 and 21 for values of th emale and female rats of the 4-week study
- results of acute toxicity studies for male and female rats and mice were reported for the oral, subcutaneous, and intravenous routes of exposure. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes. Liver, kidneys, lung,skin. See publication, photos on pages 765-772.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- no effects observed
- Description (incidence and severity):
- No erythema, scab and other irritative response were noted at the application site in any of the experimental groups including the control group of the 4-week and the 25-week-study
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 2 (4-week study) and No. 3 (25-week study), and Figures 1 and 2
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 4 and 5 (4-week study) and No. 6 (25-week study), and Figures 3 through 6
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 4 and 5 (4-week study) and No. 7 (25-week study), and Figures 3 through 6
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 12 through 14 (4-week study) and No. 15 (25-week study)
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 16 and 17 (4-week study) and No. 18 and 19 (25-week study)
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 8 and 9 (4-week study) and No. 10 and 11 (25-week study)
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- no effects observed
- Description (incidence and severity):
- no change in the albumin /globulin ratio in either study
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- See publication, Tables No. 20 (4-week study) and No. 21 (25-week study)
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Description (incidence and severity):
- behaviour was unchanged in all treated groups
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 216 mg/kg bw/day
- Based on:
- act. ingr.
- Remarks:
- urea
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect noted
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- No adverse effects were noted in subacute and subchronic dermal toxicity studies using male and female rats at 216 mg/kg bw and day.
- Executive summary:
The repeated dose dermal toxicity of urea was examined in male and female Wistar rats in a 4-week study (15 rats per dose and sex) and in a 25-week study (10 rats per dose and sex). An ointment containing urea at 0, 10, 20, and 40% was applied daily to the dorsal skin, dose levels used were 0, 56, 108, and 216 mg/kg bw and day. Examinations included observation of clinical signs and behaviour, food and water intake, body weight development, clinical chemistry, haematology, urinalysis, gross pathology, examination of organ weights, and histopathology at termination.
Several effects were seen in animals of the intermediate dose group, but there was no dose-related adverse effect or pathological change in body weights, food and water consumption, or effects on any organ, clinical chemistry, haematology or urinalysis parameters. Further, no local effects on the skin were seen at the application sites. Thus no toxicity was seen in either study at urea doses up to and including 216 mg/kg bw and day which was the NOAEL in this study (Sato et al., 1977).
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